Affinage

CD19

B-lymphocyte antigen CD19 · UniProt P15391

Length
556 aa
Mass
61.1 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD19 is a B cell transmembrane glycoprotein that functions as the principal signaling amplifier of the B cell antigen receptor (BCR), integrating complement, costimulatory, and innate immune inputs to set B cell activation thresholds and control humoral immunity. CD19 physically associates with surface immunoglobulin and Bruton's tyrosine kinase (Btk), and upon BCR engagement its cytoplasmic tyrosines Y513, Y482, and Y391 are sequentially phosphorylated by Lyn, creating docking sites for PI3K, Vav, and Lyn itself; this Lyn→CD19 amplification loop drives synergistic MAP kinase activation, sustained Akt signaling, and Ca²⁺ flux, and is essential in vivo for B1, marginal zone, and germinal center B cell differentiation (PMID:2479707, PMID:12387743, PMID:20101619, PMID:11509585). CD19 also integrates TLR9 signals via a MYD88/PYK2/LYN/PI3K/BTK/AKT axis, and its surface expression—tightly controlled transcriptionally by ZNF143, TEAD2/Mst1, and DOCK8/WASP, and post-transcriptionally by NUDT21-mediated mRNA polyadenylation and SPPL3-dependent glycosylation—directly determines the boundary between productive immunity and autoimmunity (PMID:26478008, PMID:36138187, PMID:35690611, PMID:11086109). Alternative splicing of exon 2 (regulated by SRSF3) causes protein misfolding, ER retention, loss of CD81 binding, and failure of surface trafficking, constituting a major mechanism of antigen escape from CD19-directed CAR T cell therapy in B-ALL (PMID:26516065, PMID:30104252).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    The first evidence that CD19 is not an isolated surface marker but physically and functionally coupled to the BCR came from the demonstration that anti-Ig antibodies specifically co-modulate and co-cap CD19, establishing CD19 as a component of the antigen receptor complex.

    Evidence Co-modulation and co-capping assays with 15 anti-CD19 mAbs and anti-Ig on mature B cells

    PMID:2479707

    Open questions at the time
    • Nature of the physical linkage between CD19 and sIg was unknown
    • No signaling consequences were measured
    • Whether other coreceptor components (CD21, CD81) were required for the association was not addressed
  2. 1997 High

    The question of what CD19 does to BCR signaling output was answered by showing that CD19 co-ligation with membrane Ig synergistically amplifies MAP kinase (ERK2, JNK, p38) activation, establishing CD19 as a positive signal amplifier rather than merely a physical accessory.

    Evidence MAP kinase activation assays with selective co-ligation of CD19 and CD22 with mIg on B cells

    PMID:9252120

    Open questions at the time
    • Specific CD19 residues mediating amplification were unknown
    • Kinase cascade intermediates between CD19 and MAP kinases were not fully defined
  3. 2001 High

    Multiple studies converged to define the signaling architecture downstream of CD19: CD19 is required for efficient Akt activation following BCR cross-linking, physically associates with Btk to maintain its activated state, and operates in a Lyn/CD19 amplification loop whose disruption abolishes B cell hyper-responsiveness and autoimmunity.

    Evidence Akt kinase assays in CD19-deficient cells; Co-IP of CD19 and Btk; compound CD19/Lyn and CD19/Xid knockout mouse phenotyping; Ca²⁺ flux assays

    PMID:11042164 PMID:11509585 PMID:12023340

    Open questions at the time
    • The hierarchy and kinetics of tyrosine phosphorylation on CD19 were not yet resolved
    • How the CD19/Btk interaction is regulated was unclear
  4. 2002 High

    Site-directed mutagenesis in transgenic mice demonstrated that cytoplasmic tyrosines Y482 and Y513 are essential for all major CD19 functions in vivo—B1, marginal zone, and germinal center B cell development and antibody responses—converting correlative signaling data into definitive in vivo requirements.

    Evidence CD19-knockout mice reconstituted with tyrosine-mutant CD19 transgenes; comprehensive immunological phenotyping

    PMID:12387743

    Open questions at the time
    • Individual contributions of Y482 vs Y513 were not fully separated in this study
    • Role of Y391 in vivo was not addressed
  5. 2007 High

    The discovery that CD86 costimulatory signals converge on CD19 via Lyn phosphorylation to recruit Vav and PI3K expanded CD19's role from a BCR-specific coreceptor to an integrator of costimulatory input for IgG1 class-switch regulation.

    Evidence Co-IP of CD19 with Lyn/Vav/PI3K after CD28/Ig stimulation; adoptive transfer in RAG2-deficient mice with CD86-deficient B cells

    PMID:17641017

    Open questions at the time
    • Whether other costimulatory ligands (CD80) use the same CD19-dependent pathway was not tested
    • The CD86→Lyn→CD19 pathway was shown only for IgG1 regulation
  6. 2009 High

    Genetic uncoupling of complement receptor CD21 from CD19 in knockin mice proved that the physical CD21–CD19 interaction is required for germinal center B cell survival and secondary antibody responses, validating the coreceptor complex model in vivo.

    Evidence Cr2 delta/delta gfp knockin mice; germinal center B cell survival and antibody titer measurements

    PMID:19706534

    Open questions at the time
    • Whether CD81 independently contributes to CD19 coreceptor function in this system was not dissected
    • Molecular mechanism of CD21-to-CD19 signal transfer was not defined
  7. 2010 High

    Phospho-specific antibodies resolved the temporal and spatial code of CD19 tyrosine phosphorylation: Y513 (Lyn docking) is phosphorylated first and localizes to lipid rafts; Y482 (PI3K) and Y391 (Vav) follow with distinct kinetics and raft distribution, and different BCR isotypes and co-stimuli produce distinct phosphorylation patterns.

    Evidence Phospho-specific flow cytometry; lipid raft fractionation; BCR isotype and co-stimulation comparisons

    PMID:20101619

    Open questions at the time
    • Phosphatases responsible for Y482 dephosphorylation were not identified
    • How raft partitioning of pY513 vs pY482 translates into distinct downstream outputs was not resolved
  8. 2015 High

    Two studies expanded CD19's biology beyond the BCR: CD19 was shown to be required for TLR9-induced B cell activation via a MYD88/PYK2/LYN/PI3K/BTK/AKT axis, and alternative splicing of CD19 exon 2 (regulated by SRSF3) was identified as a mechanism of resistance to CD19-directed CAR T therapy in B-ALL.

    Evidence Phospho-flow and Co-IP in CD19-deficient human B cells and patient samples; siRNA/genome editing of SRSF3 with CAR T cytotoxicity assays and relapse sample sequencing

    PMID:26478008 PMID:26516065

    Open questions at the time
    • Whether CD19 integrates other TLR signals beyond TLR9 was not tested
    • The full repertoire of splicing factors controlling exon 2 inclusion was not mapped
  9. 2018 High

    The mechanism of exon 2 skipping-mediated resistance was shown to operate via protein misfolding and ER retention rather than simple epitope loss: exon 2-deleted CD19 acquires only high-mannose glycans, colocalizes with ER chaperones, and fails to bind CD81, precluding surface trafficking.

    Evidence Pulse-chase, glycan analysis, mass spectrometry interactome, GFP-ER co-localization, ADC killing assays

    PMID:30104252

    Open questions at the time
    • Whether pharmacological chaperones could rescue surface expression of exon 2 variants was not tested
    • The structural basis of CD81 binding dependence on exon 2 was not resolved
  10. 2018 High

    CD79b/Igβ was shown to form an alternative signaling module with CD19 in Burkitt lymphoma cells lacking other BCR components, demonstrating that CD19 can participate in ITAM/PI3K-dependent survival signaling independently of the canonical BCR complex.

    Evidence CRISPR/Cas9 deletion of BCR components in Ramos cells; proximity assays; competitive growth assays

    PMID:29669863

    Open questions at the time
    • Whether this Igβ/CD19 module operates in normal B cells or only in lymphoma was not established
    • The stoichiometry and structural basis of the Igβ–CD19 interaction was not defined
  11. 2022 High

    Genome-wide CRISPR screens identified two new regulators of CD19 surface expression relevant to therapy resistance: SPPL3, whose loss causes hyperglycosylation that inhibits CAR T recognition, and NUDT21, which limits CD19 mRNA stability via polyadenylation, while ZNF143 activates the CD19 promoter.

    Evidence Genome-wide CRISPR-Cas9 screens in B-ALL cells; SPPL3/NUDT21/ZNF143 gain- and loss-of-function; glycosylation analysis; mRNA polyadenylation analysis; CAR T and blinatumomab assays; patient relapse samples

    PMID:35690611 PMID:36138187

    Open questions at the time
    • The specific glycan modifications on CD19 that impede CAR binding were not structurally resolved
    • Whether NUDT21 regulation of CD19 operates in normal B cell development was not examined
  12. 2023 High

    Cryo-EM structures of CD19 with FMC63 and SJ25C1 revealed the conformational epitope spanning exons 3–4 loops and enabled rational engineering of affinity-variant CARs, showing that binder affinity tunes antigen density sensitivity and trogocytosis propensity.

    Evidence Cryo-EM at near-atomic resolution; molecular dynamics-guided affinity variant design; CAR T functional assays

    PMID:36867678

    Open questions at the time
    • Structure of full-length CD19 including the transmembrane and cytoplasmic domains is still lacking
    • How CD19 conformational dynamics on live B cells affect epitope accessibility was not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of CD19 interaction with CD81 and CD21 in the intact coreceptor complex, the identity of phosphatases that reset CD19 tyrosine phosphorylation, whether the Igβ/CD19 alternative signaling module is physiologically relevant outside lymphoma, and how SPPL3-dependent glycosylation changes specifically impair CAR T recognition at the molecular level.
  • No structure of the CD19/CD81/CD21 coreceptor complex exists
  • Phosphatases controlling CD19 dephosphorylation are unidentified
  • Physiological relevance of Igβ/CD19 module in non-malignant B cells is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 11 R-HSA-162582 Signal Transduction 6
Partners
BTKCD21CD79BCD81LYNPIK3R1VAV1
Complex memberships
CD19/CD21/CD81/CD225 B cell coreceptor complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD19 is physically and functionally associated with surface immunoglobulin (sIg) on B cells. Anti-Ig antibodies cause specific, rapid, reversible, and unidirectional co-modulation of CD19, with anti-Ig co-capping and internalizing anti-CD19 mAb, suggesting CD19 is a component of the B cell antigen receptor complex that facilitates signal transduction by sIg-antigen complexes. Co-modulation assays, co-capping experiments with 15 CD19-specific mAbs and anti-Ig mAbs on mature B cells The Journal of experimental medicine High 2479707
1997 CD19 and CD22 have counterregulatory effects on MAP kinase (ERK2, JNK, p38) activation downstream of membrane immunoglobulin (mIg). Co-ligation of CD19 with mIg synergistically amplifies MAP kinase activation, while CD22 suppresses MAP kinase activation when cross-linked to mIg. This regulation is dependent on the proximity of these coreceptors to the antigen receptor. MAP kinase activation assays with selective co-ligation and cross-linking of CD19 and CD22 with mIg on B cells Immunity High 9252120
2001 CD19 is necessary for efficient activation of Akt kinase following BCR cross-linking or Igβ ligation in B lymphocytes. In the absence of CD19, Akt kinase activity is reduced and transient. Co-ligation of CD19 with surface immunoglobulin leads to dose-dependent augmented Akt activity, placing CD19 as a key regulator of PI3K-dependent Akt survival signaling. Akt kinase activity assays in CD19-deficient B lymphoma cells and mouse splenic B cells; co-ligation experiments The Journal of biological chemistry High 11042164
2001 CD19 deficiency suppresses the hyper-responsive B cell phenotype and autoimmunity (serum autoantibodies, glomerulonephritis) in Lyn-deficient mice, demonstrating that a CD19/Lyn amplification loop is a major regulator of B cell signaling thresholds. Tyrosine phosphorylation of Fyn and BCR-induced Ca2+ responses were dramatically reduced in CD19/Lyn double-deficient B cells. Compound knockout mouse model (CD19/Lyn double-deficient); immunological phenotyping, Ca2+ flux assays, tyrosine phosphorylation analysis Journal of immunology High 11509585
2002 CD19 cytoplasmic tyrosines Y482 and Y513 are essential for all major functions of CD19 in vivo, including differentiation of B1 and marginal zone B cells, T-dependent and -independent antibody responses, and germinal center B cell maturation. Mutation of Y482/Y513 reduces proliferation in germinal center B cells. CD19-knockout mice expressing transgenic CD19 constructs with specific tyrosine mutations; immunological phenotyping in vivo Immunity High 12387743
2002 CD19 physically associates with Bruton's tyrosine kinase (Btk) following BCR engagement in A20 B cells. CD19 expression maintains Btk in an activated state following BCR engagement, rather than being required for initial Btk phosphorylation. CD19-induced Ca2+ responses require downstream Btk function, and CD19 deficiency combined with Btk mutation (Xid) has additive inhibitory effects. Co-immunoprecipitation of CD19 and Btk; genetic compound mouse models (CD19−/− × Xid); Ca2+ flux assays; PI3K/Akt activation assays Journal of immunology High 12023340
2007 CD86 signals through CD19 to activate PI3K and increase IgG1 production in B cells. CD28/Ig-mediated signaling increases phosphorylation of Lyn and CD19 and the association of Lyn, Vav, and PI3K with CD19. This effect is absent in CD86- or CD19-deficient B cells, placing CD86→Lyn→CD19 upstream of PI3K in IgG1 regulation. Co-immunoprecipitation of CD19 with Lyn/Vav/PI3K; adoptive transfer experiments in RAG2-deficient mice with CD86-deficient B cells; in vitro stimulation assays Journal of immunology High 17641017
2009 Uncoupling CD21 (complement receptor) from CD19 via knockin mice expressing mutant receptors that bind C3 ligands but cannot signal through CD19 significantly diminishes survival of germinal center B cells and secondary antibody titers, confirming that the physical and functional interaction between CD21/CR and CD19 is necessary for coreceptor activity in humoral immunity. Knockin mouse model (Cr2 delta/delta gfp); germinal center B cell survival assays; antibody titer measurements Proceedings of the National Academy of Sciences of the United States of America High 19706534
2010 CD19 cytoplasmic tyrosines Y513, Y482, and Y391 are differentially phosphorylated during B cell activation, serving as docking sites for Lyn (Y513), PI3K (Y482), and Vav (Y391). Y513 phosphorylation occurs first, Y482 is delayed and transient. Phosphorylated Y513 localizes exclusively to lipid rafts, while pY482 and pY391 are found both inside and outside rafts. BCR isotype (IgM vs. IgG) and co-stimulation (BCR + CD40) produce distinct phosphorylation patterns affecting downstream Vav, PI3K, and Akt signaling. Phospho-specific antibodies for each CD19 tyrosine; lipid raft fractionation; flow cytometry; co-stimulation experiments European journal of immunology High 20101619
2015 Alternative splicing of CD19 mRNA, specifically skipping of exon 2, enables resistance to CART-19 immunotherapy. The splicing factor SRSF3 is involved in exon 2 retention and its levels are lower in relapsed B-ALL. Exon 2 skipping bypasses exon 2 mutations and allows expression of an N-terminally truncated CD19 variant that fails to trigger CART-19 killing but partly rescues defects associated with CD19 loss. Pull-down/siRNA experiments identifying SRSF3; genome editing to demonstrate exon 2 skipping; flow cytometry; cytotoxicity assays; sequencing of relapse samples Cancer discovery High 26516065
2015 CD19 is required for TLR9-induced B cell activation. TLR9 ligands induce phosphorylation of CD19 through a MYD88/PYK2/LYN complex, which recruits PI3K and leads to phosphorylation of BTK and AKT. Inhibition of PI3K, AKT, or BTK, as well as BTK deficiency, produces TLR9 activation defects similar to CD19 deficiency, defining a CD19/PI3K/AKT/BTK axis integrating BCR and TLR9 signaling. Phospho-flow cytometry; immunoblotting; co-immunoprecipitation in CD19-deficient B cells and CD19-knockdown cell lines; B cells from patients with 1 or 2 defective CD19 alleles The Journal of allergy and clinical immunology High 26478008
2016 Mst1 kinase positively regulates BCR signaling via transcriptional upregulation of CD19. Mst1 upregulates CD19 mRNA levels by regulating the transcription factor TEAD2, which directly binds to a consensus motif in the 3' UTR of cd19. Mst1 deficiency leads to reduced BCR signaling, defective BCR clustering and B cell spreading, and severe defects in MZ and germinal center B cell differentiation. Genetically manipulated mouse models (Mst1 knockout); total internal reflection fluorescence microscopy; RT-PCR; chromatin binding assays for TEAD2 at cd19 3' UTR Blood advances High 29296937
2018 CD19 exon 2 variants (insertion or skipping) resulting from resistance to CART therapy cause protein misfolding and retention in the endoplasmic reticulum. CD19 exon 2 variant proteins acquire ER-specific high-mannose glycans but not Golgi-processed complex glycans, colocalize with ER markers (including calnexin), and fail to bind the tetraspanin CD81 (instead associating with ER-resident chaperones). This indicates the resistance mechanism operates via surface localization failure rather than pure epitope loss. Pulse-chase assays; alpha-mannosidase inhibitor assays; GFP-fusion co-localization with ER markers; mass spectrometric profiling of CD19-interacting proteins; flow cytometry with anti-VSVg antibody; ADC killing assays Molecular and cellular biology High 30104252
2018 CD79b (Igβ) and CD19 form an alternative B cell signaling module in Burkitt lymphoma cells. In Ramos B cells lacking all other BCR components, Igβ can be expressed on the cell surface in close proximity to CD19, and signals in an ITAM-dependent manner to promote fitness and competitive growth via ITAM/PI3K signaling. CRISPR/Cas9 deletion of BCR and co-receptor genes in Ramos BL cell line; proximity assays; competitive growth assays; ITAM signaling analysis The EMBO journal High 29669863
1999 CD19 cytoplasmic signaling domain mediates growth inhibition in myeloma cells. CD19 transfectants of a myeloma cell line showed slower growth, reduced colony formation, and decreased tumorigenicity in SCID mice. A truncated CD19 lacking the cytoplasmic signaling domain did not produce growth inhibition, demonstrating that the effect requires intracellular signaling, not just surface expression. Stable transfection of CD19 vs. truncated CD19 (lacking cytoplasmic domain); in vitro growth assays; soft agar colony formation; in vivo SCID mouse tumorigenicity assay Blood High 10552966
2022 Expression of Golgi-resident intramembrane protease SPPL3 in malignant B cells regulates CD19 surface abundance and CAR T cell susceptibility. Loss of SPPL3 causes hyperglycosylation of CD19 that directly inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity. Overexpression of SPPL3 drives loss of CD19 protein and also enables resistance. This identifies post-translational glycosylation of CD19 as a mechanism of antigen escape. Genome-wide CRISPR screens; SPPL3 overexpression/knockout; glycosylation analysis; CAR T cell cytotoxicity assays in vitro Nature communications High 35690611
2022 The RNA-binding protein NUDT21 limits CD19 expression by regulating CD19 mRNA polyadenylation and stability, while the transcriptional activator ZNF143 activates the CD19 promoter. NUDT21 deletion in B-ALL cells increased CD19 surface expression and enhanced sensitivity to CD19-specific CAR-T and blinatumomab. Upregulation of NUDT21 mRNA coincided with CD19 loss at disease relapse in human B-ALL patients. Genome-wide CRISPR-Cas9 screening; NUDT21 and ZNF143 deletion/overexpression; mRNA polyadenylation analysis; CAR-T and blinatumomab functional assays; patient sample analysis Nature immunology High 36138187
2023 Cryo-EM structures of CD19 in complex with the FMC63 and SJ25C1 antibody binders were solved. FMC63's conformational epitope spans spatially adjacent but genetically distant loops in exons 3 and 4 of CD19. These structures guided molecular dynamics simulations to create lower- and higher-affinity CD19 binders, and CAR T cells with distinct binder affinities showed different antigen density requirements for cytolysis and different propensities for trogocytosis. Cryo-EM structure determination; molecular dynamics simulations; affinity-variant CAR T cell functional assays (cytolysis, trogocytosis) Science immunology High 36867678
2018 Dock8 regulates BCR signaling via CD19. Dock8 deficiency reduces WASP protein and activity levels; WASP positively regulates cd19 transcription, and Dock8 also directly regulates cd19 transcription. Dock8-deficient B cells show reduced pCD19 and pBtk levels, defective BCR clustering and B cell spreading, and disrupted memory B cell activation. Dock8 knockout mouse model; human patient peripheral blood cells; confocal and TIRF microscopy; RT-PCR for cd19 transcription; phospho-CD19 and phospho-Btk flow cytometry Blood advances Medium 29472447
1994 The Fc region of IgG1 anti-CD19 antibodies enhances cellular uptake of CD19 immunotoxins via FcγRIIa (CD32a) on B cells. IgG1-CD19 immunotoxin was ~100-fold more potent than IgG2a-IT. Removal of the Fc part equalized internalization rates. FcγRII-blocking mAbs decreased cytotoxicity of IgG1-IT but not IgG2a-IT, establishing FcγRIIa as mediating enhanced CD19 IgG1 internalization. 125I-labeled mAb binding and internalization studies; FcγRII-blocking mAbs; cytotoxicity assays with class-switch variants Cancer research Medium 7516821
2000 Small quantitative increases (15-29%) in CD19 cell surface expression in transgenic mice are sufficient to induce spontaneous autoantibody production (antinuclear Abs, rheumatoid factor, anti-DNA, anti-histone), demonstrating that CD19 expression levels directly set signaling thresholds controlling the balance between immunity and autoimmunity. CD19 transgenic mouse lines with defined surface expression increases; autoantibody profiling; comparison with human systemic sclerosis patients showing ~20% elevated CD19 Journal of immunology High 11086109
2019 Comprehensive single-site saturation mutagenesis of the CD19 extracellular domain mapped the epitopes of CD19 antibodies FMC63, 4G7-2E3, and 3B10. FMC63's conformational epitope spans spatially adjacent but genetically distant loops in exons 3 and 4. All three antibodies have partially overlapping but distinct epitopes near the B43 antibody epitope. Removal of all N-linked glycosylation sites still permitted antibody binding in a yeast display context. Comprehensive single-site saturation mutation library screening via yeast display; flow cytometric selection; epitope mapping; thermostability variant identification Biochemistry High 31702909

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. The New England journal of medicine 1682 32023374
2015 Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer discovery 1051 26516065
2018 Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 724 29849141
2016 Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. The Journal of clinical investigation 483 27571406
2012 CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Experimental hematology & oncology 427 23210908
2024 Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial. Nature medicine 356 38238616
1995 CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leukemia & lymphoma 260 8528044
2000 Quantitative genetic variation in CD19 expression correlates with autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 244 11086109
2016 Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies. Computational and structural biotechnology journal 239 27761200
2018 Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies. CNS drugs 208 30387077
2015 CAR therapy: the CD19 paradigm. The Journal of clinical investigation 181 26325036
2006 Lineage specification and plasticity in CD19- early B cell precursors. The Journal of experimental medicine 153 16505143
2009 CD19: a promising B cell target for rheumatoid arthritis. Nature reviews. Rheumatology 150 19798033
2020 CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies. Molecular therapy : the journal of the American Society of Gene Therapy 131 33010231
2021 Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia. Leukemia 129 34002027
2011 SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 128 22003072
2019 Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T. Nature communications 124 31316055
2023 Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood advances 119 35482927
2019 Toxicities of CD19 CAR-T cell immunotherapy. American journal of hematology 112 30784102
2018 B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Therapeutic advances in neurological disorders 108 29593838
2002 The physiologic role of CD19 cytoplasmic tyrosines. Immunity 104 12387743
2021 Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy. Nature communications 103 33558546
1997 Counterregulation by the coreceptors CD19 and CD22 of MAP kinase activation by membrane immunoglobulin. Immunity 95 9252120
2014 CD19-CAR trials. Cancer journal (Sudbury, Mass.) 94 24667955
2012 CD19(+)CD1d(+)CD5(+) B cell frequencies are increased in patients with tuberculosis and suppress Th17 responses. Cellular immunology 94 22361174
1989 CD19 is functionally and physically associated with surface immunoglobulin. The Journal of experimental medicine 94 2479707
2001 Cd19-dependent activation of Akt kinase in B-lymphocytes. The Journal of biological chemistry 81 11042164
2019 Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL. Blood advances 77 30890546
2005 CD19 function in central and peripheral B-cell development. Immunologic research 72 15778510
2020 Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Leukemia 68 33077866
2018 CD19 Alterations Emerging after CD19-Directed Immunotherapy Cause Retention of the Misfolded Protein in the Endoplasmic Reticulum. Molecular and cellular biology 68 30104252
2017 CD19, from bench to bedside. Immunology letters 68 28153605
2019 High TLR7 Expression Drives the Expansion of CD19+CD24hiCD38hi Transitional B Cells and Autoantibody Production in SLE Patients. Frontiers in immunology 64 31231380
2018 Continuous signaling of CD79b and CD19 is required for the fitness of Burkitt lymphoma B cells. The EMBO journal 62 29669863
2022 Antigen glycosylation regulates efficacy of CAR T cells targeting CD19. Nature communications 56 35690611
2023 CD19 CAR antigen engagement mechanisms and affinity tuning. Science immunology 55 36867678
2021 CAR T cells: Building on the CD19 paradigm. European journal of immunology 55 34196410
2014 Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation. The Journal of allergy and clinical immunology 54 24418477
2005 Diminished expression of CD19 in B-cell lymphomas. Cytometry. Part B, Clinical cytometry 49 15624204
2020 Complications after CD19+ CAR T-Cell Therapy. Cancers 47 33228221
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2015 CD19 controls Toll-like receptor 9 responses in human B cells. The Journal of allergy and clinical immunology 46 26478008
2014 New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. Journal of neuroimmunology 45 24662004
2018 CD19+ tumor-infiltrating B-cells prime CD4+ T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer. Cancer immunology, immunotherapy : CII 44 30259082
2018 Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. Scientific reports 44 30479356
2014 CD19 and CD32b differentially regulate human B cell responsiveness. Journal of immunology (Baltimore, Md. : 1950) 44 24442430
2020 Pre-sensitization of Malignant B Cells Through Venetoclax Significantly Improves the Cytotoxic Efficacy of CD19.CAR-T Cells. Frontiers in immunology 42 33362794
2019 Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL. Genomics, proteomics & bioinformatics 42 31201998
2013 Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond. Leukemia & lymphoma 41 23885836
2002 Complementary roles for CD19 and Bruton's tyrosine kinase in B lymphocyte signal transduction. Journal of immunology (Baltimore, Md. : 1950) 38 12023340
2023 Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Molecular therapy. Methods & clinical development 36 37744005
1999 Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity. Blood 36 10552966
2020 How I treat adults with advanced acute lymphoblastic leukemia eligible for CD19-targeted immunotherapy. Blood 35 31899793
2019 Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design. Biochemistry 35 31702909
2001 A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 35 11509585
2024 Aggressive Lymphoma after CD19 CAR T-Cell Therapy. The New England journal of medicine 34 39589371
2013 A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. Journal of translational medicine 34 23360526
2019 Treatment of patients with relapsed or refractory CD19+ lymphoid disease with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector: a unicentre phase I/II clinical trial protocol. BMJ open 33 31110096
2018 Dysfunction of CD19+CD24hiCD27+ B regulatory cells in patients with bullous pemphigoid. Scientific reports 32 29335495
2009 Uncoupling CD21 and CD19 of the B-cell coreceptor. Proceedings of the National Academy of Sciences of the United States of America 32 19706534
2006 Loss of CD19 expression in B-cell neoplasms. Histopathology 32 16430470
2002 Role of CD19 signal transduction in B cell biology. Immunologic research 32 12403344
2020 Deficit of circulating CD19+ CD24hi CD38hi regulatory B cells in severe aplastic anaemia. British journal of haematology 30 32311088
2019 Retargeting CD19 Chimeric Antigen Receptor T Cells via Engineered CD19-Fusion Proteins. Molecular pharmaceutics 30 31242389
2017 CD28 and 41BB Costimulation Enhances the Effector Function of CD19-Specific Engager T Cells. Cancer immunology research 30 28821531
2023 Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Molecular therapy : the journal of the American Society of Gene Therapy 29 36945773
2022 CD34+CD19-CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies. Blood 29 35421218
2021 HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. Blood advances 29 33656536
2007 CD86 regulates IgG1 production via a CD19-dependent mechanism. Journal of immunology (Baltimore, Md. : 1950) 28 17641017
2022 Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers. Cancer immunology research 27 35362043
2021 Self-driving armored CAR-T cells overcome a suppressive milieu and eradicate CD19+ Raji lymphoma in preclinical models. Molecular therapy : the journal of the American Society of Gene Therapy 27 33974997
2016 Mst1 positively regulates B-cell receptor signaling via CD19 transcriptional levels. Blood advances 26 29296937
2015 BAFF-driven autoimmunity requires CD19 expression. Journal of autoimmunity 26 26103922
2010 B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes and immunity 26 20445561
2023 Complexities in comparing the impact of costimulatory domains on approved CD19 CAR functionality. Journal of translational medicine 25 37518011
2024 Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma. EBioMedicine 24 38608514
2013 Targeting CD19 in B-cell lymphoma: emerging role of SAR3419. Cancer management and research 24 24023523
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